Investigation and risk stratification of systemic sclerosis heart involvement

Primary systemic sclerosis primary heart involvement (pSSc-HI) is one of the leading causes of death in SSc. Sensitive testing suggests that the majority of patients have subclinical involvement; however, there is little understanding of its pathogenesis, dynamics and importantly, the optimal approach to clinical detection and management. Identifying the at-risk patient for more intensive monitoring and management is thus essential. By applying sensitive tools, including implantable loop recorder (ILR) and cardiovascular magnetic resonance (CMR) the thesis proposes to provide a comprehensive assessment of pSSc-HI and to identify clinical and cardiac serum markers that could aid early identification of patient at risk of pSSc-HI. The thesis also evaluates the predictive value of subclinical CMR abnormalities for the development of cardiovascular (CV) outcomes and assesses for any interval change of CMR detected pSSc-HI and whether disease-modifying anti-rheumatic (DMARD) or vasodilator treatment can alter the course of pSSc-HI. The thesis demonstrates significant ILR findings especially in a poor prognosis group, supporting therefore the use of ILR in SSc patients. CMR-extracellular volume (ECV), marker of diffuse fibrosis and cardiac biomarkers high-sensitivity troponin I (hs-TnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) associate with ILR abnormalities, suggesting their potential value in detecting pSSc-HI arrythmias. Three distinctive CMR findings are identified: diffuse and focal fibrosis and reduced myocardial perfusion. Skin score, digital ulcers and cardiac biomarkers are associated with CMR abnormalities, whilst CMR-ECV and NT-proBNP predict the development of future CV outcomes. Finally, no significant interval change in CMR parameters is observed, albeit a higher likelihood of CMR deterioration is noted in a poor prognosis group, whilst DMARD and vasodilator treatment do not seem to alter the course of CMR pSSc-HI. The results of the thesis are thus providing a first step towards risk stratification of pSSc-HI, that will support future larger studies.